crossing96/oncoscreening huggingface dataset:
Tumor necrosis factor‑related apoptosis‑inducing ligand as a therapeutic option in urothelial cancer cells with acquired resistance against first‑line chemotherapy.	Patients with urothelial carcinoma frequently fail to respond to first‑line chemotherapy using cisplatin and gemcitabine due to development of resistant tumor cells. The aim of the present study was to investigate whether an alternative treatment with tumor necrosis factor‑related apoptosis‑inducing ligand (TRAIL) that induces tumor cell death via the extrinsic apoptotic pathway may be effective against chemotherapy‑resistant urothelial cancer cell lines. The viability of the urothelial cancer cell line RT112 and its chemotherapy‑adapted sublines was investigated by MTT assay. The expression of anti‑apoptotic proteins was determined by western blotting and the individual roles of cellular inhibitor of apoptosis protein (cIAP)1, cIAP2, x‑linked inhibitor of apoptosis protein (XIAP) and induced myeloid leukemia cell differentiation protein (Mcl‑1) were investigated by siRNA‑mediated depletion. In particular, the bladder cancer sublines that were resistant to gemcitabine and cisplatin were cross‑resistant to TRAIL. Resistant cells displayed upregulation of anti‑apoptotic molecules compared with the parental cell line. Treatment with the second mitochondrial activator of caspases (SMAC) mimetic LCL‑161 that antagonizes cIAP1, cIAP2 and XIAP resensitized chemoresistant cells to TRAIL. The resensitization of tumor cells to TRAIL was confirmed by depletion of antiapoptotic proteins with siRNA. Collectively, the findings of the present study demonstrated that SMAC mimetic LCL‑161 increased the sensitivity of the parental cell line RT112 and chemotherapy‑resistant sublines to TRAIL, suggesting that inhibiting anti‑apoptotic molecules renders TRAIL therapy highly effective for chemotherapy‑sensitive and ‑resistant urothelial cancer cells.	bladder
circRIP2 accelerates bladder cancer progression via miR-1305/Tgf-β2/smad3 pathway.	BACKGROUND: Increasing evidences indicate that circular RNAs exert critical function in regulating bladder cancer progression. However, the expressive patterns and roles of circular RNAs in bladder cancer remain less investigated. METHODS: circRIP2 was identified and evaluated by RNA-sequencing and qPCR; in vitro effects of circRIP2 were determined by CCK8, clone forming, wound healing and trans-well assays; while mice subcutaneous tumor model was designed for in vivo analysis. Western blot, RNA pulldown assay, miRNA capture and dual luciferase assessment were applied for mechanistic studies. RESULTS: circRIP2 was identified as a conserved and dramatically repressed circular RNA in bladder cancer. Patients that displayed higher circRIP2 expression negatively associate with the grade, stage, metastasis as well as outcome of bladder cancer. In vitro and in vivo studies suggest that circRIP2 enables to promote bladder cancer progression via inducing EMT. Regarding the mechanism, we performed RNA-sequencing analysis, RNA pulldown with biotin-labeled circRIP2-specific probe, dual luciferase reporter assay. It was found that circRIP2 enables to sponge miR-1305 to elevate Tgf-β2 in bladder cancer, and inducing EMT via Tgf-β2/smad3 pathway. Blocking Tgf-β2 in bladder cancer deprives circRIP2 induced cancer progression and EMT. CONCLUSIONS: Taken together, our study provides the first evidence that circRIP2 expresses differentially in bladder cancer and negatively along with the cancer progression; effective circRIP2 activity accelerates bladder cancer progression via inducing EMT by activating miR-1305/Tgf-β2/smad3 pathway. The research implies that circRIP2 might be a potential biomarker and therapeutic target for bladder cancer patients.	bladder
Fluid intake and clinicopathological characteristics of bladder cancer: the West Midlands Bladder Cancer Prognosis Programme.	OBJECTIVE: Between 10 and 20% of bladder cancer patients who are diagnosed with nonmuscle-invasive bladder cancer will progress to muscle-invasive disease. Risk of progression depends on several factors at diagnosis including age, tumour stage, grade, size and number, and the presence or absence of carcinoma in situ. Fluid intake may be related to these factors. METHODS: Data of 1123 participants from the West Midlands Bladder Cancer Prognosis Programme were used. Data collection was via a semistructured questionnaire, and case report forms were used to collect clinicopathological data. Fluid intake was measured for six main categories: alcoholic fluids, hot fluids, fruit fluids, milk, fizzy drinks, and water, and converted into quintile variables. Multilevel mixed-effects linear regression was performed for every beverage category per clinicopathological variable and corrected for age, gender, and smoking status. RESULTS: Age at diagnosis was distributed differently amongst those in different total fluid intake quintiles (predicted means 71.5, 70.9, 71.5, 69.9, and 67.4, respectively) and showed a significant inverse linear trend in alcohol (P < 0.01), hot fluids (P < 0.01), and total fluids intake (P < 0.01), in nonmuscle-invasive bladder cancer patients. CONCLUSION: Our results suggest an inverse association for alcohol intake and total fluid intake with age at diagnosis. These results should be confirmed by future studies, alongside a possible (biological) mechanism that could influence tumour growth, and the effect of micturition frequency.	bladder
Bladder mulberry-like fibroepithelial polyp with calcification and squamous cell metaplasia mimicking bladder carcinoma: case report and literature review.	Fibroepithelial polyps (FEPs) are a rare, benign disease in the urinary system. We present a clinical case of a 34-year-old woman with a symptomatic bladder tumor. Cystoscopy showed a mulberry-like mass with calcification in the bladder trigone. After transurethral resection, histopathology showed an FEP in the bladder with calcification and squamous cell metaplasia. The patient was discharged from hospital 3 days after surgery. We review the recent literature to summarize the clinical manifestations, treatments, and prognosis of bladder FEPs.	bladder
Refinement Surgical Technique, and Perioperative and Functional Outcomes in Patients With Robotic Intracorporeal Hautmann Orthotopic Neobladder.	OBJECTIVE: To illustrate our refinement technique for robotic intracorporeal orthotopic Hautmann neobladder with adherence to open surgical principles and evaluate perioperative and functional outcomes. PATIENTS AND METHODS: Robot-assisted radical cystectomy with intracorporeal Hautmann orthotopic neobladder was performed by the same surgeon in 40 patients with bladder cancer from November 2017 to March 2019. Baseline demographics, pathologic data, 90-day complications, and functional outcomes at both 6 and 12 months were evaluated with questionnaire and urodynamic analysis. RESULTS: Median follow-up was 14 months (range 4-20). Median operative time was 320 (230-500) minutes, and the estimated blood loss was 300 (100-2000) mL. No conversion to the open technique was reported. The overall 90-day complication rate was 45%, and the high-grade complication rate was only 10%. The daytime satisfactory continence rate was 90% at both 6 months (30 patients) and 12 months (20 patients), while the night-time satisfactory continence rate was 76.7% and 80.0% at 6 months and 12 months, respectively. One patient underwent clean intermittent catheterization. The cohort had minimal postvoid residual volume, normal compliance, and a mean capacity of 328.7 cm(3) (range 170-500) at 6 months postoperatively. CONCLUSION: Our preliminary data indicate that robotic intracorporeal Hautmann neobladder configuration is a feasible surgical technique and can achieve a low pressure and sufficient capacity for satisfactory early voiding patterns. Refinement of the stepwise process can effectively decrease the time of the operation. Long-term functional and oncological outcomes remain to be evaluated with longer follow-up and more cases.	bladder
Intraoperative use of single dose of nonsteroidal anti-inflammatory drugs was not associated with cancer recurrence and mortality after bladder cancer surgery: a retrospective study.	BACKGROUND: Recently, intraoperative use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been demonstrated to be associated with improved outcomes after surgery for several cancers; however, the effect of intraoperative NSAIDs use on bladder cancer (BCa) is not known. Therefore, the present study investigated the association between intraoperative NSAIDs use and oncological outcomes after radical cystectomy (RC). METHODS: We retrospectively analyzed 248 patients with BCa who underwent RC. Kaplan-Meier analysis and a Cox regression model were used to evaluate the association between intraoperative NSAIDs (parecoxib) use and oncological outcomes after RC. RESULTS: After excluding 63 patients, 82 of the remaining 185 patients received parecoxib during surgery. In the parecoxib group, the overall recurrence rate did not decrease significantly (P=0.310). Time to recurrence, cancer-specific mortality, and overall mortality were not significantly different between the groups. Kaplan-Meier analysis showed no association of the intraoperative use of parecoxib with an improved recurrence-free survival (RFS) or overall survival (OS) (P=0.431, P=0.185, respectively). Similarly, the multivariate analysis model showed no association between the administration of parecoxib and RFS [hazard ratio (HR), 0.964; 95% confidence interval (CI), 0.599-1.551, P=0.878] or OS (HR, 1.043; 95% CI, 0.621-1.750; P=0.875). In these patients, elevated preoperative neutrophil-lymphocyte ratio (NLR) was demonstrated to be associated with RFS and OS. CONCLUSIONS: The present study found that intraoperative parecoxib use was not associated with improved outcome after BCa surgery. Prospective, randomized trials should be performed to further evaluate the results of this study.	bladder
Massive Neobladder Stones in Postcystectomy Patient Lost to Follow Up.	A 59-year-old man with a history of muscle-invasive bladder cancer status post cystectomy with neobladder creation presented to the Emergency Department with a 4-month history of lower abdominal pain, dysuria, and intermittent hematuria. He was found to have 2 massive bladder stones on CT scan, measuring 12 × 10.5 × 14 cm and 6.5 × 7.5 × 10 cm. Stones were successfully removed via open neocystolithotomy. Stones were composed of a mixture of calcium phosphate (80%) and calcium carbonate (20%).	bladder
Robotic-assisted radical cystectomy: the first multicentric Brazilian experience.	The objective of this study is to report the first multicentric Brazilian series and learning curve of robotic radical cystectomy (RARC) with related intra- and postoperative outcomes. We retrospectively analyzed 37 RARC prospectively collected at four different centers in Brazil, from 2013 to 2019. We analyzed the patient's demographics, pathological tumor, and nodal status, as well as intra- and postoperative outcomes. Statistical analysis was performed with the IBM (SPSS version 25) software. Overall, 86% were male, and the median age was 69 years. 83% had muscle-invasive bladder cancer, and 17% a high-grade, recurrent non-muscle-invasive tumor. The median operative time was 420 min with 300 min as console time. Median blood loss was 350 ml and transfusion rate was 10%. In 68% of the cases, we performed an intracorporeal Bricker urinary diversion, 24% intracorporeal neobladder, and 8% ureterostomy. Six patients (16%) had a Clavien 1-2, 8% had Clavien 3, 2.5% had a Clavien 4, and 5% had Clavien 5. The median length of hospital stay was 7 days. The final pathological exam pointed out pT0 in 16%, pT1 in 8%, pT2 in 32%, ≥ pT3 in 27%, and 16% pTis. 95% had negative surgical margins. The survival at 30, 90, and 180 days was 98%, 95%, and 95%, respectively. To our knowledge, this is the first multicentric series of RARC reporting the learning curve in Brazil; even if still representing a challenging procedure, RARC could be safely and effectively faced by experienced surgeons at centers with high volumes of robotic surgery.	bladder
Luteolin suppresses bladder cancer growth via regulation of mechanistic target of rapamycin pathway.	Luteolin is a natural flavonoid with strong anti-oxidative properties that is reported to have an anti-cancer effect in several malignancies other than bladder cancer. In this study, we describe the effect of luteolin on a human bladder cancer cell line, T24, in the context of the regulation of p21, thioredoxin-1 (TRX1) and the mechanistic target of rapamycin (mTOR) pathway. Luteolin inhibited cell survival and induced G2/M cell-cycle arrest, p21 upregulation and downregulation of phospho(p)-S6, which is downstream of mTOR signaling. Luteolin also upregulated TRX1 and reduced intracellular reactive oxygen species production. In a subcutaneous xenograft mouse model using the rat bladder cancer cell line, BC31, tumor volumes were significantly decreased in mice orally administered luteolin compared to control. Immunohistochemical analysis revealed that increased p21 and decreased p-S6 expression were induced in the luteolin treatment group. Moreover, in another in vivo N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN)-induced rat bladder cancer model, the oral administration of luteolin led to a trend of decreased bladder tumor dimension and significantly decreased the Ki67-labeling index and p-S6 expression. Furthermore, the major findings on the metabolism of luteolin suggest that both plasma and urine luteolin-3'-O-glucuronide concentrations are strongly associated with the inhibition of cell proliferation and mTOR signaling. Moreover, a significant decrease in the squamous differentiation of bladder cancer is attributed to plasma luteolin-3'-glucuronide concentration. In conclusion, luteolin, and in particular its metabolized product, may represent another natural product-derived therapeutic agent that acts against bladder cancer by upregulating p21 and inhibiting mTOR signaling.	bladder
Tumor Infiltrating Neutrophils Are Enriched in Basal-Type Urothelial Bladder Cancer.	BACKGROUND: Urothelial bladder cancers (UBCs) are distinct in two main molecular subtypes, namely basal and luminal type. Subtypes are also diverse in term of immune contexture, providing a rationale for patient selection to immunotherapy. METHODS: By digital microscopy analysis of a muscle-invasive BC (MIBC) cohort, we explored the density and clinical significance of CD66b(+) tumor-associated-neutrophils (TAN) and CD3(+) T cells. Bioinformatics analysis of UBC datasets and gene expression analysis of UBC cell lines were additionally performed. RESULTS: Basal type BC contained a significantly higher density of CD66b(+) TAN compared to the luminal type. This finding was validated on TCGA, GSE32894 and GSE124305 datasets by computing a neutrophil signature. Of note, basal-type MIBC display a significantly higher level of chemokines (CKs) attracting neutrophils. Moreover, pro-inflammatory stimuli significantly up-regulate CXCL1, CXCL2 and CXCL8 in 5637 and RT4 UBC cell lines and induce neutrophil chemotaxis. In term of survival, a high density of T celsl and TAN was significantly associated to a better outcome, with TAN density showing a more limited statistical power and following a non-linear predicting model. CONCLUSIONS: TAN are recruited in basal type MIBC by pro-inflammatory CKs. This finding establishes a groundwork for a better understanding of the UBC immunity and its relevance.	bladder
Current Understanding of Urachal Adenocarcinoma and Management Strategy.	PURPOSE OF REVIEW: The aim of this review is to sum up the state of the art of urachal carcinoma (UC) in order to easily guide clinicians. RECENT FINDINGS: UC is a rare and aggressive disease with consequent few data about diagnosis and treatment. Dates are mainly based on retrospective trial and case reports with limited prospective trial. Clinical presentation is not specific, often with urinary symptoms. Diagnosis is mainly based on CT scan and MRI, useful to evaluate local invasion and nodal status and to detect the presence of distant metastases. Therefore, biopsy is needed to obtain histological confirmation. Surgery is the gold standard for localized disease, while different chemotherapy schemes have been used in metastatic setting. Novel findings based on mutational analysis of the tumor include the use of biological treatment, such as cetuximab, and immunotherapy, such as atezolizumab, with satisfactory responses, suggesting that personalized treatment could be the most suitable option for UC.	bladder
Management of Muscle-invasive Bladder Cancer in the 2020s: Challenges and Perspectives.	Despite an increased use of neoadjuvant and adjuvant chemotherapy, the long-term survival rates after radical cystectomy or trimodal therapy (TMT) for muscle-invasive bladder cancer (MIBC) remain basically unchanged for decades. Detection and effective treatment of micrometastatic disease are still a clinical dilemma. Assessment of circulating tumor DNA in combination with improved imaging modalities may improve the prediction of micrometastatic disease. Different genetic subtypes of MIBC show varying degrees of chemosensitivity. Further progress needs to be made in order to develop a common molecular classifier that can be used easily for daily clinical decision making. With the advent on immuno-oncology, bladder-sparing protocols are on the rise as an alternative to surgery. The extent of transurethral bladder tumor resection has a marked impact on the response rates to TMT and neoadjuvant chemotherapy. This review focuses on strategies regarding how to integrate surgery, radiotherapy, and molecular-based systemic treatment for improved oncological outcomes of patients with MIBC. PATIENT SUMMARY: Effective treatment of micrometastatic disease is the key to improved oncological outcomes in muscle-invasive bladder cancer and requires a multidisciplinary approach.	bladder
Structural maintenance of chromosomes 2 is identified as an oncogene in bladder cancer in vitro and in vivo.	Taurine upregulated gene 1 (TUG1) has been found to promote bladder cancer cell growth in our recent research. In this study, TUG1-depleted bladder cancer cells were used to identify potent players in bladder cancer. Human gene expression arrays were used for transcriptome profiling of TUG1-depleted bladder cancer cells. Cell proliferation was analyzed by MTT assay. Cell apoptosis and cell cycle were analyzed by flow cytometry. Colony formation assay was used to observe the changes of colony formation rates. Xenograft formation assay was performed in nude mice. Immunohistochemical staining was used to test the gene expression levels in tissues from bladder cancer patients. We found that deregulated genes were strongly enriched in cell cycle or pathways in cancer in TUG1-depleted bladder cancer cells. Structural maintenance of chromosomes 2 (SMC2) was inhibited after TUG1 knockdown. The depletion of TUG1 or SMC2 led to G2/M phase arrest in bladder cancer cells. SMC2 depletion inhibited bladder cancer cell proliferation, promoted apoptosis, decreased colony formation, and reduced tumor growth in xenograft nude mice. Overexpression of SMC2 restored the growth of TUG1-depleted cells. The expression levels of SMC2 were higher in human bladder cancer tissues than that in paired normal tissues. Our data suggest that SMC2 is an oncogene in bladder cancer and depletion of SMC2 might have potential therapeutical significance in bladder cancer.	bladder
Prediction of recurrence and progression in patients with T1G3 bladder cancer by gene expression of circulating tumor cells.	OBJECTIVE: To investigate the role of gene expression of circulating tumor cells (CTCs) as noninvasive prognostic markers in patients with high risk nonmuscle invasive bladder cancer. MATERIALS AND METHODS: We identified all patients with TIG3 urothelial bladder cancer (UBC) at our institution since 2016.The study included 100 patients with T1G3 UBC and 50 healthy volunteers. CTCs were isolated from blood using immunomagnetic separation and gene expression was performed using 10 bladder cancer associated genes, namely; KRAS, EPCAM, CD133, CD44, mTOR, SURVIVIN, AKT, PI3K, VEGF, and TP53. Gene expression of CTCs was correlated to time to first recurrence and time to progression using Kaplan-Meier curves. RESULTS: There was strong negative correlation between CTCs-positive patients and time to first recurrence and time to progression. Significant differences in expression levels of specific genes were observed that can predict recurrence and progression of T1G3 UBC. CONCLUSION: CTCs appear to be noninvasive methods of predicting disease recurrence and progression in patients with high- risk nonmuscle invasive bladder cancer; therefore, studying their molecular profiling may improve prediction of recurrence and progression. Further studies are invited for more in-depth investigation to consolidate our initial results.	bladder
The value of transurethral thulium laser en bloc resection combined with a single immediate postoperative intravesical instillation of pirarubicin in primary non-muscle-invasive bladder cancer.	The objective of this study was to evaluate which patients might benefit from a single immediate postoperative intravesical instillation (SII) compared to maintenance intravesical instillations (MII) in primary non-muscle-invasive bladder cancer (NMIBC) after transurethral en bloc resection of bladder tumors (ERBT). A total of 141 patients with primary NMIBC who underwent ERBT with thulium laser between January 2012 and May 2016 were retrospectively enrolled. All the patients were categorized into two groups based on the duration of postoperative intravesical instillation of pirarubicin (THP): single intravesical instillation (SII) group, patients received a single immediate postoperative intravesical instillation of THP (30 mg), and maintenance intravesical instillations (MII) group, patients received a 1-year MII of THP (30 mg). Prognosis and recurrence data of each group were analyzed. One hundred and four (73.8%) patients received MII, and other 37 (26.2%) patients received SII. There was no significant difference in recurrence-free survival (RFS) between the two groups (P = 0.105). Following recurrence risk-stratified analysis, patients with high recurrence risk who accepted SII had a significantly lower RFS rate than those who received MII (P = 0.027). However, there were no significant differences in RFS rate between the two groups in patients with low and intermediate recurrence risk. In the multivariate analysis, the number of tumors was found to be an independent prognostic factor for RFS in NMIBC patients [hazard ratio, 5.665; 95% confidence interval (CI), 2.577-12.454; P < 0.001]. SII seems not to be inferior to MII in patients with initial low-risk and intermediate-risk NMIBC after ERBT.	bladder